1. Field of the Invention
This invention is related to the field of meiotic recombination of partially homologous DNA sequences.
2. Description of the Related Art
Genetic recombination is dependent on the formation of a near perfectly paired heteroduplex joint molecule containing complementary strands from two homologous DNA duplexes. Reduced homology between substrate molecules decreases the efficiency of recombination. A striking example of this can be seen during interspecific crosses between Escherichia coli and Salmonella typhymurium. The genomes of these two bacterial species are diverged by approximately 16%. At this level of heterology the frequency of recombination during conjugational crosses is reduced by up to 5 orders of magnitude. The barrier to recombination is largely dependent on the activity of the mismatch repair system The “disrupted species barrier” and “chromosomal instability” phenotypes, seen in bacterial mismatch repair mutants, are thought to result from a failure to prevent interactions between homeologous (closely related but non-identical) DNA sequences. This process has been termed antirecombination, although its molecular basis remains unclear. The existence of this activity has led to the proposal that the mismatch repair system is involved in controlling the fidelity of genetic exchanges. By only permitting crossovers between truly homologous sequences, such a process would suppress ectopic interactions between dispersed homologous sequences and thereby avoid potentially lethal chromosome rearrangements. Hence, the recognition of mismatches in duplex DNA may play a role in maintaining the structural integrity of chromosomes.
Many of the elements of the long-patch mismatch repair system that are believed to be involved in antirecombination have been organism of which the enzymatic mismatch repair system is defective or has been inactivated transitorily, particularly by saturation, for a time to obtain recombination between the DNA sequences. Although the specification envisages the possibility of performing such recombinations in bacteria, yeasts, plant or animal cells, in fact the experimental data provided only demonstrate such recombinations in bacteria of different genera, where the recombinations are achieved by a process of mitotic recombination.
In eukaryotes, the enzymatic mismatch repair systems are more complex than in prokaryotes. Also, the enzymatic mismatch repair systems involved in meiosis are to some extent different from those involved in mitosis. It was therefore not predictable that the technique generally described in the aforesaid European patent specification could be successfully applied to eukaryotic cells undergoing meiosis.